Research articles

Neutrophil elastase speeds up the progression of lung cancer by degrading insulin receptor substrate-1 and thereby phosphatidylinositol 3-kinase. This is the first description of a secreted proteinase gaining access to the inside of a cell to alter intracellular signaling (pages 161–163).

Colleen Delaney and colleagues have developed a new culture system for umbilical cord blood progenitors that improves myeloid engraftment in cord blood transplants using a Notch ligand–mediated ex vivo expansion strategy. The study demonstrates rapid hematopoietic engraftment in a NOD/SCID mouse model and a phase 1 myeloablative cord blood transplantation trial. The strategy could lead to better clinical outcomes as a result of reduced morbidity and mortality.

The protein kinase mTOR is known to contribute to cancer development. However, existing drugs targeting mTOR, such as rapamycin, have not been very effective at inhibiting cancer cell survival and also have the unwanted side effect of immunosuppression. Studying preclinical models of leukemia driven by the BCR-ABL oncogene, Matthew Janes et al. now show that a new mTOR inhibitor—which unlike previous ones is an ATP competitive inhibitor that targets the active site of the enzyme—can overcome these drawbacks.

Variation in the IL-7 receptor is associated with susceptibility to multiple sclerosis. Jingwu Zhang and his colleagues provide an explanation. They show that the cytokine IL-7 regulates the surival and proliferation of T helper type 17 cells—a cell type known to be involved in the pathogenesis of multiple sclerosis. The findings suggest that IL-7 antagonism could be useful in individuals with autoimmune diseases such as multiple sclerosis (pages 166–168).